‘Imfinzi used as perioperative gastric cancer treatment’

Patient selection and multidisciplinary care crucial given the risk of micrometastasis and recurrence

Stage 3 gastric cancer recurs in nearly half of patients…highlighting the need for reimbursement coverage

“Surgical outcomes in gastric cancer have steadily improved, but recurrence remains the biggest challenge in patients with stage 2 and 3 disease. It is time to adopt a therapeutic strategy that addresses micrometastasis even before surgery.”

Professor Hyoung-il Kim of the Division of Gastrointestinal Surgery and Professor Minkyu Jung of Medical Oncology at Severance Hospital recently explained so in an interview with DailyPharm, noting that perioperative therapy based on ‘Imfinzi (durvalumab)’ could become a new option for managing recurrence in gastric cancer.

(From the left) Professor Minkyu Jung of Medical Oncology and Professor Hyoung-il Kim of the Division of Gastrointestinal Surgery at Severance Hospital

Gastric cancer is one of the most common cancers in Korea. Although overall survival is on the rise with the increased early detection through the National Cancer Screening Program, in patients with advanced-stage disease, recurrence remains the biggest factor determining long-term prognosis.

In particular, patients with resectable stage 2 or 3 gastric cancer still face a considerable risk of recurrence even after curative surgery and postoperative adjuvant chemotherapy. In real-world clinical practice, approximately 20% to 30% of stage 2 patients and more than half of stage 3 patients are known to experience recurrence.

In many cases, cure is often difficult once recurrence is confirmed. For this reason, how well recurrence can be reduced during the initial treatment phase is considered a key determinant of treatment success.

Experts point to micrometastasis as a major cause of such recurrence, as it is difficult to detect with conventional imaging tests. Micrometastasis refers to minimal residual disease (MRD), in which tumor cells have already spread systemically through the bloodstream or lymphatic system at the time of diagnosis but remain undetectable with existing imaging tests. In other words, cancer cells too small to be detected by preoperative CT or laparoscopic examination may already have spread via the blood or lymphatic vessels, eventually causing the cancer to recur after the operation.

Until now, the standard treatment for resectable gastric cancer has been surgery followed by postoperative chemotherapy. Although postoperative chemotherapy has helped reduce recurrence risk, concerns have continued that it has limitations in sufficiently controlling micrometastasis in patients at high risk of recurrence.

Against this backdrop, interest is rising in strategies that begin treatment before surgery, when tumor burden is relatively low and immune function is preserved to suppress micrometastasis early. In particular, the rising potential of perioperative immunotherapy has influenced the gastric cancer treatment paradigm.

In March this year, AstraZeneca’s immunotherapy ‘Imfinzi (durvalumab)’ obtained an indication as perioperative therapy for patients with resectable gastric cancer and gastroesophageal junction adenocarcinoma. The treatment strategy involves administering Imfinzi in combination with perioperative FLOT chemotherapy (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) in patients with resectable gastric cancer or gastroesophageal junction adenocarcinoma, followed by maintenance treatment with Imfinzi monotherapy.

In the global Phase III MATTERHORN trial, which served as the basis for approval, perioperative therapy with Imfinzi reduced the risk of disease progression, recurrence or death by 29% compared with existing treatment. In the overall survival (OS) analysis, it also reduced the risk of death by 22%, demonstrating a survival benefit. It also showed significantly improved results versus the control group across key endpoints, including event-free survival (EFS) and pathological complete response (pCR).

Surgery remains the cornerstone of curative treatment for gastric cancer. However, both in Asia and globally, there is growing recognition that surgery alone is insufficient to achieve cure in many gastric cancer patients. The MATTERHORN trial showed that administering immunotherapy plus FLOT before surgery, followed by curative resection and additional treatment, can meaningfully improve long-term treatment outcomes.

The two professors said, “The goal of treating resectable gastric cancer is not simply to complete surgery successfully, but to reduce recurrence and improve long-term survival. Imfinzi perioperative therapy is meaningful in that it enables early management of micrometastasis, and we expect its use in real-world clinical practice to expand based on appropriate patient selection and multidisciplinary care.”

They added, “In particular, for stage 2 and 3 patients at high risk of recurrence, the clinical value of a new treatment option is significant. Ultimately, reimbursement needs to be set so that patients can timely recieve treatment opportunities.”

Q. For high-risk patients, strategies to enhance the completeness of surgery appear to be crucial. From this perspective, what are the current gaps in gastric cancer treatment strategies that require improvement?"

[Professor Hyoung-il Kim]: The core goal of gastric cancer surgery is to precisely remove cancer tissue and lymph nodes while minimizing damage to normal tissue. In recent years, advances in laparoscopy, fluorescence-guided technology, and robotic surgery have continued to improve surgical precision.

However, no matter how many advances are made in terms of surgical techniques, there are areas that cannot be addressed by surgery alone. The most significant recent shift in addressing these limitations is the emergence of perioperative therapy based on immunotherapy. While chemotherapy was historically aimed at delaying recurrence, the current focus has evolved toward reducing the recurrence rate itself and increasing the likelihood of long-term survival.

Q. In the MATTERHORN trial, Imfinzi perioperative therapy significantly improved the primary endpoint of event-free survival (EFS). How do you think these results could change patient prognosis in practice?

Professor Minkyu Jung of Medical Oncology at Severance Hospital

[Professor Minkyu Jung]: Various studies of immunotherapy-based perioperative therapy have been conducted in gastric cancer, but some did not produce results as strong as expected.

By contrast, the global Phase III MATTERHORN trial was encouraging, as it is the first study to demonstrate clinical benefit of immunotherapy-based perioperative therapy in patients with resectable gastric cancer.

The combination of Imfinzi and FLOT significantly improved EFS by reducing the risk of disease progression, recurrence, or death from any cause by 29%, and also showed a meaningful improvement in OS.

I also consider it important that pCR was approximately 2.7 times higher than in the control group. It is highly significant that the preoperative administration of the Imfinzi-FLOT combination has led to a pCR rate of approximately 19.2% by effectively managing invisible micrometastases and minimal residual disease before surgery.

As patients who achieve pCR are generally considered to have the best treatment response, a favorable long-term prognosis can also be expected. Another point worthy of attention is that a relatively consistent treatment effect was observed, regardless of PD-L1 expression status.

Q. A multidisciplinary strategy seems very important in perioperative therapy. How are treatment decisions made at Severance Hospital?

Professor Hyoung-il Kim of the Division of Gastrointestinal Surgery at Severance Hospital

[Professor Hyoung-il Kim]: With the introduction of perioperative therapy, changes are needed across the entire treatment process. For perioperative therapy to be applied effectively, it is important to accurately determine which patients are most likely to benefit from this treatment.

To do this, a system must be in place to identify patients who need preoperative immunotherapy at the right time, refer them from surgery to medical oncology, and ensure that preoperative treatment and surgery proceed in an integrated manner. 

In this process, multidisciplinary care plays a very important role, as specialists from surgery, medical oncology, radiology, pathology, and other fields need to jointly evaluate the patient’s stage and recurrence risk to determine the optimal treatment sequence.

From the patient’s perspective, it may feel unfamiliar to come to the hospital for surgery and then be told to receive immunotherapy before surgery. Therefore, the process of building trust with the patient by clearly explaining the need for treatment and its expected benefits through multidisciplinary collaboration is also important for successful treatment.

Q. When applying Imfinzi perioperative therapy in practice, it seems important to determine which patients should be prioritized. Beyond simple resectability, what factors are comprehensively assessed when deciding whether and how to treat patients?

[Professor Minkyu Jung]: In Korea and Japan, gastric cancer is often detected relatively early, so preoperative treatment does not need to be applied to all patients. Representative high-risk groups include patients whose tumors are shown on imaging to have deeply invaded the gastric wall or patients suspected of having lymph node metastasis.

These patients have a higher risk of recurrence and may be more likely to benefit from preoperative treatment. In addition, the need for preoperative treatment may be greater in gastroesophageal junction cancer, as surgery can be complex and complete resection may be difficult due to anatomical characteristics.

Q. What is your view on the need for reimbursement for Imfinzi perioperative therapy?

[Professor Hyoung-il Kim]: Since this perioperative approach has confirmed its meaningful clinical benefits in a Phase III study, it is well worth reviewing its reimbursement coverage. In particular, because nearly half of patients with stage 3 gastric cancer experience recurrence even after surgery, rapid reimbursement coverage is needed so that high-risk patients can be identified first and given timely treatment opportunities.

[Professor Minkyu Jung]: At present, there are no reimbursed treatment options that can be used as perioperative therapy in patients with resectable gastric cancer. Especially in high-risk patient groups, even when a treatment has demonstrated clinical value, treatment choices may be limited due to financial burden. Therefore, I believe institutional support that reflects clinical need is necessary so that patients do not miss treatment opportunities due to economic burden.

Q. What efforts do you think are needed to improve Korea’s gastric cancer treatment outcomes?

[Professor Minkyu Jung]: Korea has a well-established system for early detection of gastric cancer through the national screening program, but blind spots still exist. Patients who have not undergone regular screening and visit the hospital only after symptoms appear are often diagnosed at stage 3 or 4. I think finding these high-risk groups more effectively will be an important task going forward. In addition, as new treatment options such as immunotherapies and targeted therapies continue to emerge, research is also needed to develop personalized treatment strategies tailored to each patient’s characteristics.

[Professor Hyoung-il Kim]: In gastric cancer, treatment goals differ depending on the timing of detection and disease stage. For patients detected early, maintaining quality of life as much as possible after treatment is important. For patients detected at an advanced stage, reducing recurrence and improving survival are the key challenges. Surgical techniques continue to evolve through robotic surgery, fluorescence-guided surgery, and other advances, but recently, the importance of drug therapy has grown in areas that were difficult to address with surgery alone. Should effective drug therapies continue to advance, we may be able to bring patients previously deemed unsuitable for surgery into the range of surgical treatment.